Pesticidal compositions

ABSTRACT

A liquid pesticidal composition, which is substantially free of water, comprising a hydrophobic pesticide or mixture of pesticides dissolved in an organic solvent and comprising as surfactants (a) a castor oil ethoxylate having 30-50 mol ethoxylate, (b) a branched C 8 -C 18  alcohol ethoxylate having 5-10 mol ethoxylate, and (c) a tristyrenephenol-ethoxylate having 8-30 mol ethoxylate, or its phosphate or salt thereof. The compositions also include gels having a viscosity of 500 to 20,000 mPas and comprising additionally a gelling agent.

CROSS-REFERENCE TO RELATED APPLICATIONS

Not applicable.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable.

REFERENCE TO MICROFICHE APPENDIX

Not applicable.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to storage stable, liquid, pesticidalcompositions, the preparation of such compositions and a method of usingsuch compositions to combat pests or as plant growth regulators.

2. Description of the Related Art

Alkylphenol ethoxylates, for example nonylphenol ethoxylates, andalkylbenzene sulfonates and its salts, for example dodecylbenzenesulfonate calcium salt, are commonly used and well known surfactants inwater-emulsifiable pesticidal compositions. Some of these surfactantsare not entirely satisfactory; in particular with respect to theirecological and toxicological properties. There is still a need forfurther water-emulsifiable or water soluble, liquid, homogeneouspesticidal compositions which are storage stable, ecological andtoxicological favorable and which have good pesticidal efficacy.

Fatty alcohol ethoxylates, e.g. C₁₀-C₁₄alcohol ethoxylates(EP-A-400,585) and tristyrenephenol-ethoxylates (EP-A-102,003) have beenproposed, both in combination with alkylbenzene sulfonates, assurfactants in water-emulsifiable pesticidal compositions. Combinationsof castor oil ethoxylate, fatty alcohol ethoxylate, (e.g. tridecanolethoxylate), tristyrene phenyl ethoxylate and alkylbenzene sulfonatehave been disclosed as surfactants in aqueous microemulsions (DE 36 24910).

BRIEF SUMMARY OF THE INVENTION

It has been found that the combination of a castor oil ethoxylate with abranched C₈-C₁₈ alcohol ethoxylate and a tristyrenephenol-ethoxylate isa very advantageous surfactant system for water-emulsifiable orwater-soluble pesticidal compositions; the novel compositions arestorage stable, easy to apply, ecological and toxicological favorableand have good pesticidal efficacy.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Not applicable.

DETAILED DESCRIPTION OF THE INVENTION

Accordingly, the present invention provides a water-emulsifiable orwater-soluble, storage stable, liquid, pesticidal composition, which issubstantially free of water, comprising a hydrophobic pesticide ormixture of pesticides dissolved in an organic solvent and comprising assurfactants

(a) a castor oil ethoxylate having 30-50 mol ethoxylate,

(b) a branched C₈-C₁₈ alcohol ethoxylate having 5-10 mol ethoxylate, and

(c) a tristyrenephenol-ethoxylate having 8-30 mol ethoxylate, or itsphosphate or salt thereof.

Suitable salts with bases are, for example, metal salts, such as alkalimetal or alkaline earth metal salts, for example sodium, potassiumcalcium or magnesium salts, or salts with ammonia or an organic amine,such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-loweralkylamine, for example ethyl-, diethyl-, triethyl- ordimethyl-propylamine, or a mono-, di- or tri-hydroxy-lower alkylamine,for example mono-, di- or tri-ethanolamine.

The compositions also include gels having a viscosity of 500 to 20,000mPas and comprising additionally a gelling agent.

The compositions according to the invention are stable for at least 12months at 25° C. They are very well miscible, with water, even at higherconcentrations.

The surfactants mentioned above can be prepared by methods known per se;they are also commercially available. Preferred are surfactants, wherein

(a) the castor oil ethoxylate has 36-40 mol, preferably 36-37 molethoxylate;

(b) the branched C₈-C₁₈ alcohol ethoxylate is isotridecanol ethoxylatehaving 5-10 mol, preferably 6-8 mol ethoxylate;

(c) the tristyrenephenol-ethoxylate has 16-18 mol ethoxylate.

It may be advantageous to add additionally an alkylbenzene sulfonate orits salt, preferably dodecylbenzene sulfonate calcium salt in an amountof 1 to 10%, preferably 2 to 4% by weight in relation to the volume ofthe composition.

The composition of the invention is substantially free of water, i.e.the amount of water is less that 0.5%. Some commercially availablematerials may contain a small amount of water, which, when more thanabout 0.1% can be removed for example in a separator.

In another aspect of the invention the composition is a gel with aviscosity of 500-20,000 mPas; preferably 800 to 10,000 mPas andparticularly 1000-5000 mPas. The viscosity of the composition can bemeasured using for example a BROOKFIELD viscosimeter with spindles 1 to3 at 30 rpm. In this case the composition additionally has to contain agelling agent, for example oxypropylated cellulose, precipitated orfused silica (hydrophobisized or non-hydrophobisized), gelatine,polysaccharides, tetramethyl decyne diol, ethoxylated dialkyl phenol,methylated clay, propylene carbonate, hydrogenated castor oil,ethoxylated vegetable oil, sodium benzoate and hexanediol. Preferredgelling agent is oxypropylated cellulose. Gels are particularly suitablefor pesticides packed into water soluble bags or sachets, which quicklydissolve when put into the water.

The organic solvents wherein the pesticide has to be dissolved may bewater-immiscible or water miscible or a mixture thereof. Suitablewater-immiscible solvents in which the pesticides may be dissolved arealiphatic and aromatic hydrocarbons such as hexane, cyclohexane,benzene, toluene, xylene, mineral oil or kerosene, mixtures orsubstituted naphthalenes, mixtures of mono- and polyalkylated aromaticscommercially available under the registered trademarks SOLVESSO andSHELLSOL and PETROL SPEZIAL, halogenated hydrocarbons such as methylenechloride, chloroform and o-dichlorobenzene; phthalates, such as dibutylphthalate or dioctyl phthalate; ethers and esters, such as ethyleneglycol monomethyl or monoethyl ether, fatty acid esters; lactones suchas butyrolactone, ketones, such as cyclohexanone; plant oils such ascastor oil, soybean oil, cottonseed oil and possible methyl estersthereof; as well as epoxidised coconut oil or soybean oil. Preferredwater-immiscible solvents are aliphatic and aromatic hydrocarbons, fattyacid esters (e.g. WITCONOL 2309), dipropyleneglycol monomethylether(e.g. DOWANOL DPM) and castor oil. Suitable water-miscible solvents inwhich the pesticides may be dissolved are alcohols and glycols, such asethanol, ethylene glycol, strongly polar solvents, such asN-methyl-2-pyrrolidone, tetramethylurea, gamma-butyrolactone,dimethylsulfoxide, N,N-dimethylacetamide and dimethylformamide; preferred areN-methyl-2-pyrrolidone and gamma-butyrolacone.

Suitable pesticides are those which are substantially insoluble in water(hydrophobic), but soluble in the organic solvent. The term pesticide isunderstood to encompass herbicides, insecticides, acaricides,nematicides, ectoparasiticides, fungicides and plant growth regulators.With respect to their chemical constitution, these pesticides may belongto a very wide range of compound classes. Examples of compound classesto which the suitable pesticide may belong are: acylalanines,haloacetanilides, triazole derivatives, phosphoric acid esters,pyrethroids, benzilic acid esters, polycyclic halogenated hydrocarbons,diphenyl ether derivates, formamidines, strobilurines,aryloxyphenoxy-alkanoic acid derivatives. Examples of suitableindividual compounds of the above mentioned compound classes are listedbelow. Where known, the common name is used to designate the individualcompounds (q.v. the Pesticide Manual, 10th edition, 1994,British CropProtection Council).

Haloacetanilides: Dimethachlor, Metolachlor, Pretilachlor,2-chloro-N-(1-methyl-2-methoxyethyl) -acet-2,6-xylidide, Alachlor,Butachlor, Propachlor, Dimethenamid.

Diphenyl ether derivates: Bifenox, 4-(4-Pentyn-1-yloxy)diphenylether,Acifluorfen, Oxyfluorfen, Fluoroglycofen-ethyl, Fomesafen,cis-trans-(±)2-ethyl-5-(4-phenoxy-phenoxymethyl)-1,3-dioxolane(“diofenolan”).

Phenoxypropionic acid derivatives: Fluazifop-butyl, Haloxyfop-methyl,Haloxyfop-(2-ethoxyethyl), Fluorotopic, Fenoxapropethyl,Quizalofop-ethyl, Propaquizafop, Diclofop-methyl.

Acylalanines: Furalaxyl, Metalaxyl, R-Metalaxyl, Benzoylprop ethyl,Benalaxyl, Oxadixyl, Flamprop methyl.

Triazole derivatives: Difenoconazole, Etaconazol, Propiconazole,Penconazole, Triadimefon, Epoxiconazole, Tebuconazole, Bromuconazole,Fenbuconazole, Cyproconazole.

Phosphoric acid esters: Piperophos, Anilofos, Butamifos, Azamethiphos,Chlorfenvinphos, Dichlorvos, Diazinon, Methidathion, Azinphos ethyl,Azinphos methyl, Chlorpyrifos, Chlorthiofos, Crotoxyphos, Cyanophos,Demeton, Dialifos, Dimethoate, Disulfoton, Etrimfos, Famphur,Flusulfothion, Fluthion, Fonofos, Formothion, Heptenophos, Isofenphos,Isoxathion, Malathion, Mephospholan, Mevinphos, Naled, Oxydemetonmethyl, Oxydeprofos, Parathion, Phoxim, Pyrimiphos methyl, Profenofos,Propaphos, Propetamphos, Prothiophos, Quinalphos, Sulprofos, Phemephos,Terbufos, Triazophos, Trichloronate, Fenamipos, Isazophos,s-benzyl-o,o-diisopropylphosphorothioate, Edinphos, Pyrazophos.

Pyrethroids: Allethrin, Bioallethrin, Bioresmethrin, Cyhalotrin,Cypermethrin, α-Cypermethrin, φ-Cypermethrin, Deltamethrin,Fenpropathrin, Fenvalerate, s-Fenvalerate, Flucythrinate, Fluvalinate,Permethrin, Pyrethrine, Resmethrin, Tetramethrin, Tralomethrin,Ethophenprox, Cyfluthrin, Cycloprothrin, Tefluthrin, Flufenprox,Silafluofen, Bifenthrin, Fenfluthrin, Bromfenprox.

Benzilic acid esters: Brompropylate, Chlorbenzylate, Chlorpropylate.

Polycyclic halogenated hydrocarbons: Aldrin, Endosulfan.

Strobilurines: Kresoxim-methyl, Azoxystrobin (BAS 490F),Methoxyimino-{2-[1-(3-trifluoromethyl-phenyl) -ethylideneaminooxymethyl]-phenyl}-acetic acid methyl ester.

Miscellaneous: Tridemorph, Bromoxynil, Carboxin, Prochloraz, Propargite,Dicamba, Fenpiclonil, Fenpropimorph, Fenpropidin, Fludioxonil,Pymetrozine, Pyrifenox, Pyriproxyfen, Trinexapac-ethyl, Fluazinam.

Preferred pesticides are

herbicides, as Propaquizafop, Piperophos and Propanil;

fungicides, asMethoxyimino-{2-[1-(3-trifluoromethyl-phenyl)-ethylideneaminooxymethyl]-phenyl}-aceticacid methyl ester, Propiconazole, Cyproconazole, Fluazinam, Metalaxyl orR-Metalaxyl (enantiomer of Metalaxyl), or a mixture thereof;

plant growth regulators, as Trinexapac-ethyl.

Suitable concentrations in relation to the composition are (% weight pervolume of the total composition; 1000 g per liter correspond to 100%)

of the hydrophobic pesticide or mixture of pesticides: 1 to 99%,preferably 10 to 90% and 10 to 60%;

of the organic solvent: 1 to 96%, preferably 10 to 80% and 20 to 70%;

of the surfactants: 3 to 80%, preferably 5 to 40% and 10 to 30%; whereinof

surfactant (a): 1 to 30%, preferably 2 to 20%,

surfactant (b): 1 to 40%, preferably 2 to 20%,

surfactant (c): 1 to 20%, preferably 2 to 15%;

of the gelling agent: 0.1 to 10% preferably 0.5 to 5%.

It may be advantageous to combine the pesticide or mixture of pesticideswith a safener.

Another object of the invention is a process for preparing a liquidpesticidal composition as herein described, by intimateley mixing,optionally by warming, until a homogeneous phase is achieved.

In another aspect of the invention the composition is an aqueous spraymixture.

Before the application, the composition of the invention may be dilutedwith water by simple mixing at ambient temperature in order to prepare a‘ready to use’ mixture for spraying.

This spray mixture may be an aqueous emulsion or a solution or asuspension, depending on the kind of composition. The resulting spraymixtures are stable, i.e. they remain as a homogeneously emulsifiedphase, as a solution or as a homogeneously distributed suspension onstanding without agitation for at least one hour to 12 hours or evenmore. Preferred concentrations of the spray mixture are 0.1 to 5%, morepreferred 0.5 to 2% pesticide in relation to the spray mixture.

Further aspects of the invention include a method of preventing orcombatting infestation of plants or animals by pests and regulatingplant growth by diluting the composition with water and applying apesticidally effective amount to the plant, animal or locus as desired.

PREPARATION EXAMPLES

The following Examples illustrate the invention in more detail. Theregistered trademarks and other designations denote the followingproducts:

(a) EMULSOGEN EL® castor oil-36-37 EO

(b) GENAPOL X-080® (HOECHST) Isotridecanol-8 EO GENAPOL X-060® (HOECHST)Isotridecanol-6 EO

(c) SOPROPHOR BSU® (RHÒNE-P) Tristyrenephenole-16 EO SOPROPHOR 3D33®(RHÔNE-P) Tristyrenephenol-poly-EO-phosphate

WITCONOL 2309® Fatty acid methylester

PETROL SPEZIAL 200® Mixture of aromatic hydrocarbons

KLUCEL M® Oxypropylated cellulose (gelling agent)

DOWANOL DPM® Dipropyleneglycol monomethylether (mixture of isomers)

EO=ethyleneoxide

PO=propyleneoxide

% in weight per volume of the total composition (i.e.1000 g·per litercorrespond to 100%) The components are intimately mixed, optionally bywarming, until a homogeneous phase is achieved.

% component type Example 1 100    Propaguizofop herbicide 5.0 EMULSOGENEL ® surfactant (a) 30.0  GENAPOL X-060 ® surfactant (b) 5.0 SOPROPHORBSU ® surfactant (c) 10.0  1-Methyl-2-pyrrolidone solvent 40.0  PETROLSPEZIAL 200 solvent Example 2 14.5  Piperophos herbicide 25.0  Propanilherbicide 4.0 EMULSOGEN EL ® surfactant (a) 12.0  GENAPOL X-060 ®surfactant (b) 4.0 SOPROPHOR BSU ® surfactant (c) 47.0 Dipropyleneglycol monomethyl ether solvent Example 3 9.3 R-Metalaxylfungicide 4.0 EMULSOGEN EL ® surfactant (a) 12.0  GENAPOL X-060 ®surfactant (b) 4.0 SOPROPHOR BSU ® surfactant (c) 5.0Gamma-Butyrolactone solvent 27.0  Fatty acid methyl ester Me C 6-10solvent Example 4 20.0  R-Metalaxyl fungicide   30.0 g Fluazinamfungicide 6.0 EMULSOGEN EL ® surfactant (a) 6.0 GENAPOL X-060 ®surfactant (b) 6.0 SOPROPHOR BSU ® surfactant (c) 30.0 Gamma-Butyrolactone solvent rest Aromatic Solvent 230 solvent Example 510.0  R-Metalaxyl fungicide   20.0 g Fluazinam fungicide 6.0 EMULSOGENEL ® surfactant (a) 6.0 GENAPOL X-060 ® surfactant (b) 6.0 SOPROPHORBSU ® surfactant (c) 30.0  Gamma-Butyrolactone solvent rest AromaticSolvent 230 solvent Example 6 20.0  R-Metalaxyl fungicide   40.0 gFluazinam fungicide 3.0 EMULSOGEN EL ® surfactant (a) 3.0 GENAPOLX-060 ® surfactant (b) 3.0 SOPROPHOR BSU ® surfactant (c) 2.0 dodecylbenzene sulfonate Ca-salt surfactant 15.0  Gamma-Butyrotactone solventrest Aromatic Solvent 230 solvent Example 7 26.3  Trinexapac-ethyl plantgrowth regulator 11.4  EMULSOGEN EL ® surfactant (a) 7.1 GENAPOL X-060 ®surfactant (b) 10.0  SOPROPHOR BSU ® surfactant (c) 45.2  WITCONOL 2309sovent Example 8 (Gel) 26   Trinexapac-ethyl plant growth regulator11.4  EMULSOGEN EL ® surfactant (a) 7.1 GENAPOL X-060 ® surfactant (b)10.0  SOPROPHOR BSU ® surfactant (c) 1.0 Klucel M ® gelling agent restDOWANOL DPM ® solvent Viscosity: ca. 2900 mPas (Spindle 3/30 rpm)

All the compositions according to the examples are stable for at least12 months at 25° C.

After diluting with water the compositions form an emulsion or,depending on the pesticide, solvent and concentration, a clear solution.Both the emulsions and solutions are stable without agitation for atleast one to 12 hours or even more.

What is claimed is:
 1. A liquid pesticidal composition comprising ahydrophobic pesticide or mixture of pesticides dissolved in an organicsolvent and comprising as surfactants (a) a castor oil ethoxylate having30-50 mol ethoxylate (b) a branched C₈-C₁₈ alcohol ethoxylate having5-10 mol ethoxylate, and (c) a tristyrenephenol-ethoxylate having 8-30mol ethoxylate, or its phosphate or salt thereof said composition beingsubstantially free of water, wherein said organic solvent is selectedfrom the group consisting of a water-miscible solvent, awater-immiscible solvent, and mixtures thereof, wherein saidwater-immisible solvent is selected from aliphatic and aromatichydrocarbons, halogenated hydrocarbons, phthalates, ethers and esters,fatty acid esters, lactones, ketones, plant oils, methyl esters of saidplant oils, epoxidized coconut oil, epoxidized soybean oil and mixturesthereof; and wherein said water-miscible solvent is selected from thegroup consisting of alcohols, glycols, N-methyl-2-pyrrolidone,tetramethylurea, gamma-butyrolactone, dimethylsulfoxide,N,N-dimethylacetamide, N,N-dimethylformamide, and mixtures thereof;whereby said composition is capable of being stably stored for a periodof at least one year at 25° C.
 2. The composition according to claim 1,wherein the castor oil ethoxylate (a) has 36-40 mol ethoxylate.
 3. Thecomposition of claim 2 wherein the castor oil ethoxylate (a) has 36-37mol ethoxylate.
 4. The composition according to claim 1, wherein thebranched C₈-C₁₈ alcohol ethoxylate (b) is isotridecanol ethoxylatehaving 5-10 mol ethoxylate.
 5. The composition of claim 4 wherein thebranched C₈-C₁₈ alcohol ethoxylate (b) is isotridecanol ethoxylatehaving 6-8 mol ethoxylate.
 6. The composition according to claim 1,wherein the tristyrenephenol-ethoxylate (c) has 16-18 mol ethoxylate. 7.The composition according to claim 1 which is a gel having a viscosityof 500 to 20,000 mPas and comprising additionally a gelling agent. 8.The composition according to claim 7, wherein the concentration of thegelling agent is 0.1 to 10% by weight in relation to the volume of thecomposition.
 9. The composition of claim 8 wherein said gelling agent ispresent in said composition at a concentration of 0.5 to 5% in relationto the volume of the composition.
 10. The composition according to claim7 having a viscosity of 800 to 10,000 mPas.
 11. The composition of claim10 having a viscosity of 1000-5000 mPas.
 12. The composition accordingto claim 7 wherein the gelling agent is selected from the groupconsisting of oxypropylated cellulose, precipitated or fused silica(hydrophobisized or non-hydrophobiszed), gelatine, polysaccharides,tetramethyl decyne diol, ethoxylated dialkyl phenol, methylated clay,propylene carbonate, hydrogenated castor oil, ethoxylated vegetable oil,sodium benzoate and hexanediol.
 13. The composition according to claim12, wherein the gelling agent is oxypropylated cellulose.
 14. Thecomposition according to claim 1, wherein the organic solvent iswater-immiscible.
 15. The composition according to claim 1, wherein theorganic solvent is water-miscible.
 16. The composition according toclaim 1, wherein the pesticide is a herbicide.
 17. The composition ofclaim 16 wherein said pesticide is a herbicide and is selected from thegroup consisting of Propaquizafop, Piperaphos, and Propanil.
 18. Thecomposition according to claim 1, wherein the pesticide is a fungicide.19. The composition of claim 18 wherein said pesticide is a fungicideand is selected from the group consisting ofmethoxyimino-{2-[1-(3-trifluoromethyl-phenyl)ethylideneaminooxymethyl]-phenyl}acetic acid methyl ester, Propiconazole, Cyproconazole, Fluazinam,Metalaxyl or R-Metalaxyl, and mixtures thereof.
 20. The compositionaccording to claim 1, wherein the pesticide is a plant growth regulator.21. The composition of claim 20 wherein said pesticide isTrinexapac-ethyl.
 22. The composition according to claim 1, wherein theconcentration of the pesticide or mixture of pesticides is 1 to 99% byweight in relation to the volume of the composition.
 23. The compositionaccording to claim 22, wherein the concentration of the pesticide ormixture of pesticides is 10 to 90% in relation to the volume of thecomposition.
 24. The composition of claim 23 wherein said pesticide ispresent in said composition at a concentration of 10 to 60% in relationto the volume of the composition.
 25. The composition according to claim1, wherein the concentration of the organic solvent is 1 to 96% byweight in relation to the volume of the composition.
 26. The compositionaccording to claim 25, wherein the concentration of the organic solventis 10 to 80% by weight in relation to the volume of the composition. 27.The composition of claim 26 wherein said organic solvent is present insaid composition at a concentration of 20 to 70% in relation to thevolume of the composition.
 28. The composition according to claim 1,wherein the concentration of the surfactants is 3 to 80% by weight inrelation to the volume of the composition.
 29. The composition accordingto claim 28, wherein the concentration of the surfactants is 5 to 40% byweight in relation to the volume of the composition.
 30. The compositionof claim 29 wherein said surfactants are present in said composition ata concentration of 10 to 30% in relation to the volume of thecomposition.
 31. The composition according to claim 1, furthercomprising an alkylbenzene sulfonate or a salt thereof.
 32. Thecomposition of claim 31 wherein said alkylbenzene sulfonate or its saltis dodecylbenzene sulfonate calcium salt.
 33. The composition of claim1, wherein the organic solvent is selected from aliphatic and aromatichydrocarbons, fatty acid esters and dipropyleneglycol monomethylether.34. The composition of claim 1, wherein the organic solvent is selectedfrom the group consisting of N-methyl-2-pyrrolidone andgamma-butyrolactone or a mixture thereof.
 35. A process for preparing aliquid pesticidal composition according to claim 1 by intimately mixing,optionally by warming, said pesticide or pesticides, said organicsolvent, and said surfactants (a), (b), and (c) until a homogeneousphase is achieved.
 36. An aqueous microemulsion or solution prepared bymixing the composition according to claim 1 with water.
 37. A method ofpreventing or combatting infestation of plants or animals by pests andregulating plant growth by diluting the composition according to claim 1with water and applying a pesticidally effective amount to the plant,animal or locus.
 38. A liquid pesticidal composition comprising ahydrophobic pesticide or mixture of pesticides dissolved in an organicsolvent and comprising a mixture of surfactants consisting essentiallyof (a) a castor oil ethoxylate having 30-50 mol ethoxylate; (b) abranched C₈-C₁₈ alcohol ethoxylate having 5-10 mol ethoxylate; (c) atristyrenephenol-ethoxylate having 8-30 mol ethoxylate, or its phosphateor salt thereof, and (d) optionally an alkylbenzenesulfonate or a saltthereof; said composition being substantially free of water, wherebysaid composition is capable of being stably stored for a period of atleast one year at 25° C.
 39. An aqueous microemulsion or solutionprepared by mixing the composition according to claim 38 with water. 40.A method of preventing or combatting infestation of plants or animals bypests and regulating plant growth by diluting the composition accordingto claim 38 with water and applying a pesticidally effective amount tothe plant, animal or locus.